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US 4,072,746 AGranted
3-Amino-5-(pyridinyl)-2(1H)-pyridinones
AssigneeSterling Drug Inc.
InventorsGeorge Y. Lesher, Chester J. Opalka, Jr.
Life of this patent
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AssigneeSterling Drug Inc.
InventorsGeorge Y. Lesher, Chester J. Opalka, Jr.
Estimating the term…
Compounds useful as cardiotonic agents are 1-R-3-Q-5-PY-2(1H)-pyridinones (I) where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, Q is amino (preferred), lower-alkylamino, di-(lower-alkyl)amino or NHAc, Ac is lower-alkanoyl or lower-carbalkoxy, and PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. The corresponding compounds where Q is nitro, carbamyl, cyano, halo or hydrogen are useful as intermediates and those where Q is hydrogen or cyano also are useful as cardiotonic agents. Said compounds are prepared: by reacting .alpha.-PY-.beta.-(R.sub.1 R.sub.2 N)acrolein (II) with malonamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinamide (Ia) and reacting Ia with a reagent capable of converting carbamyl to amino to produce 3-amino-5-PY-2(1H)-pyridinone (Ib); by reacting II or .alpha.-PY-malonaldehyde (II') with .alpha.-cyanoacetamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinonitrile (III) and partially hydrolyzing III to produce Ia; and, by heating 1,2-dihydro-2-oxo-5-PY-nicotinic acid (IV) with a mixture of concentrated sulfuric acid and concentrated nitric acid to produce 3-nitro-5-PY-2(1H)-pyridinone (Ic) and then either reducing Ic to produce Ib or first reacting Ic with an alkylating agent to produce 1-R'-3-nitro-5-PY-2(1H)-pyridinone (Id) and reducing Id to produce 1-R'-3-amino-5-PY-2(1H)-pyridinone (Ib) where R' is lower-alkyl or lower-hydroxyalkyl. Other derivatives of I where Q is amino are shown.
A 1-R-3-Q-5-PY-2 (1H)-pyridinone having the formula ##STR4## where PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents, R is hydrogen, lower-alkyl or lower-hydroxyalkyl and Q is nitro, amino, lower-alkylamino di-(lower-alkyl)amino, or NHAc where Ac is lower-alkanoyl or lower-carbalkoxy, or pharmaceutically-acceptable acid-addition salt thereof.
A 1-R-3-Q-5-PY-2 (1H)-pyridinone having the formula ##STR5## where PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents, R is hydrogen, lower-alkyl or lower-hydroxyalkyl and Q is nitro, lower-alkylamino, di-(lower-alkyl)amino, or NHAc where Ac is lower-alkanoyl or lower-carbalkoxy, or pharmaceutically-acceptable acid-addition salt thereof.
A 1-R-3-amino-5-PY-2 (1H)-pyridinone having the formula ##STR6## where PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents and R is hydrogen, lower-alkyl or lower-hydroxyalkyl, or pharmaceutically-acceptable acid-addition salt thereof.
3-Amino-5-(4-pyridinyl)-2 (1H)-pyridinone .
A cardiotonic composition for increasing cardiac contractility, said composition comprising a pharmaceutically-acceptable inert carrier and, as the active component thereof, an effective amount of a cardiotonic 1-R-3-Q-5-PY-2 (1H)-pyridinone having the formula ##STR7## where PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents, R is hydrogen, lower-alkyl or lower-hydroxyalkyl and Q is amino, lower-alkylamino, di-(lower-alkyl)amino or NHAc where Ac is lower-alkanoyl or loer-carbalkoxy, or pharmaceutically-acceptable acid-addition salt thereof.
The method for increasing cardiac contractility in a patient requiring such treatment which comprises administering orally or parenterally in a solid or liquid dosage form to such patient an effective amount of a cardiotonic 1-R-3-Q-5-PY-2 (1H)-pyridinone having the formula ##STR8## where PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents, R is hydrogen, lower-alkyl or lower-hydroxyalkyl and Q is amino, lower-alkylamino, di-(lower-alkyl) amino or NHAc where Ac is lower-alkanoyl or lower-carbalkoxy, or pharmaceutically acceptable acid-addition salt thereof.
Dependencies are inferred from the claim text.